Nutritionally, L-ascorbic acid is a very important nutrient, and this single substance or a salt or a derivative thereof is added to a large number of animal feedstuffs.
Particularly in recent years, livestock such as cattle and pigs, and useful marine animals such as rainbow trout, sweet fish, carp, sea bream, salmon, eel, yellow tail, globefish, flatfish, tuna, horse mackerel and prawn are bred or raised at high density. Also, dogs and cats are prevented from running off and are left in noisy places. Accordingly, these animals are inevitably subject to stress. Under such a breeding environment, these animals suffer from stress even in a normal temperature state.
Therefore, the requirement for ascorbic acid is considered to be high as compared with the case of normal breeding conditions. Furthermore, the lack in intake of ascorbic acid causes phenomena such as a loss in body weight, a reduction in immunity and an increase in morality, and incurs enormous economic damage to breeders. Particularly, under a high temperature environment in summer or under a low temperature environment in winter, the stress is intensified and the economic damage increases.
In order to reduce the stress, ascorbic acid has been added to feed for various kinds of animals. However, the L-ascorbic acid in general is prone to oxidation decomposition, and is swiftly deactivated even if it is added to feed. Accordingly, because of this problem, the effect is difficult to maintain. Particularly, in recent years, the heating-type granulating machine commonly used in feed production, such as a pellet mill and an extruder, uses a high temperature as the raw material temperature. Accordingly, other problems are also caused such that L-ascorbic acid in general is rapidly decomposed. Furthermore, because of its poor absorptivity, satisfactory effects cannot be provided even if it is added to feed or the like.
A general technique for solving these problems is to coat a fine grain of inexpensive ascorbic acids and blend the grains with feed. This technique is proposed, for example, in JP-A-52-15812 (the term "JP-A" as used herein means an "unexamined published Japanese patent application"), JP-A-53-127819, JP-A-54-109962, JP-A-54-154514, JP-A-55-4913, JP-A-57-59803, JP-A-57-85317, JP-A-58-205461, JP-A-59-44327, JP-A-63-164864, JP-A-63-258813, JP-A-64-3118, JP-A-64-3119, JP-A-1-500113, JP-A-1-296953 and JP-A-2-46259.
The coating techniques disclosed in these patent publications are common in that the coated ascorbic acid particles are finely granulated to a particle size of 1 mm or less. This prevents the coated particles from fracturing during the crushing step in the production process of feed or the like. As a result, the surface area is large and oxygen in the air readily permeates therein. This gives rise to a problem in that the coated L-ascorbic acid is easily oxidation decomposed in the production and distribution process of feed in a high-temperature pressure molding machine for processing feed.
Accordingly, a method of adding a stabilized L-ascorbic acid derivative to feed that resists oxidation, such as L-ascorbic acid-2-sulfate, has been proposed. For example, JP-A-49-24783 discloses a method of adding ascorbic acid-2-benzoate, ascorbic acid-2,6-dipalmitate, ascorbic acid-3-palmitate, ascorbic acid-3-stearate, ascorbic acid-3,6-distearate or ascorbic acid-2-phosphate, to artificial feed for silkworms.
Among these, ascorbic acid-3-palmitate, ascorbic acid-3-stearate, ascorbic acid-3,6-distearate and ascorbic acid-2-phosphate are substances which are incapable of exhibiting satisfactory stability against heat or oxidation. However, in the production conditions of silkworm feed, the nutrient components including an ascorbic acid are generally processed at a mild temperature of 65.degree. C. or lower. Therefore, stability is not a problem in the case of silkworm feed. However, recent production processes of feed in a high-temperature molding machine include processing at 70.degree. C. or higher for imparting water resistance, and almost all of the above-described ascorbic acids are disadvantageously decomposed due to the high temperature.
Furthermore, although L-ascorbic acid-2-sulfate, L-ascorbic acid-2-benzoate and ascorbic acid-2,6-dipalmitate are stable against heat or oxidation, they yet have a problem in that conversion by an intracorporeal enzyme into ascorbic acid occurs with difficulty in some animals and the ascorbic acid activity cannot be satisfactorily exerted.
On the other hand, the stress reaction of animals is closely related to the degree of change in various environments where the animals are living, more specifically, a change in environmental factors such as temperature, light, nutrients or breeding density. When the environmental change is small, animals adjust their metabolism without causing a large change in the internal metabolic control mechanism. However, when the environmental change is large, animals can difficultly adapt their metabolism to the change within a short period, and try to put into effect a qualitatively different metabolic control for sustaining and continuing life.
In general, it is known that as the environmental change is larger, the stress reaction that is generated in the animal body intensifies (as described by Yousef, M. K., Stress Physiology in Livestock, Vol. I & II, CRC Press (1985); Young B. A. et al., J. Animal Science, 67, 2426-2432 (1989); Yamada, M. and Tanaka, M., Proc. XIX World's Poultry Congress, 1992, pp. 43-47; Siegel, H. S., Br. Poult. Sci., 36, 3-22 (1995); and Yamada et al., Proc. 10th European Poultry Nutrition Symposium, 1995, pp. 373-374).
One example of the effect of ambient temperature on the physiological and production functions of homeotherms such as livestock and poultry is reported by Yamada, Dobutsu Seisan to Kankyo Chosetsu, Shinpan, Seibutsu Kankyo Chosetsu Handbook (Animal Production and Environmental Control, New Version, Biological Environment Control Handbook), pp. 234-248 (1995). More specifically, in the temperature region of from 18 to 26.degree. C., domestic fowl actively exercises its laying function and does not suffer from any outstanding stress reaction. However, if the ambient temperature enters the region of from 26 to 32.degree. C., the breathing function or behavior form starts changing and signs of stress reaction are observed. If the ambient temperature reaches the region of from 32 to 36.degree. C., the degree of temperature stress becomes large. Accompanying it, the breathing turns into panting breath, the hydroposia or diet behavior becomes very unusual and the laying function is extremely reduced to thereby cause serious economic damage in poultry farming. If the ambient temperature reaches 36.degree. C. or higher, not only the breathing form but also important physiological functions such as the thermoregulation function indispensable to sustain life start to become affected, and the nature of various functions are altered to cope with the life crisis.
In the above-described state, the sustainment of life is a most important issue and therefore, domestic fowl suppress the normal biological substance synthesizing function and accelerate the synthesis of stress proteins to undergo biophylaxis to the extent possible. In this way, the stress reaction in the living body changes to accompany the change in ambient temperature. Also, the physiological constituent factors of the stress reaction include a change in the concentration of biological components related to important metabolic functions and the change in the activity of enzymes contiguous to the substance conversion. In particular, the appearance of enzymatic activity closely related to the biological energy metabolism or appearance of stress proteins for the purpose of biophylaxis serves as a physiological index for assessing the degree of the stress reaction.
The change in metabolic function involves a large number of metabolic pathways such as the saccharometabolism, lipid metabolism and amino acid metabolism in the liver or kidney, and the dismutation metabolism between carbohydrates and amino acids. LDH and MDH are related to the saccharometabolism, and AspAT is related to the carbohydrate and amino acid metabolism. Thus, these are important enzymes. It has recently been reported that an increase in the concentration of LDH, MDH or AspAT activity in blood indicates a biological stress reaction from the aspect of metabolic function. Furthermore, suppression of the stress reaction is a very important matter in breeding livestock with high added value.
The stress protein has several molecular species and the molecular species which is produced depends on the property of the stress reaction. Appearance of the stress protein 80-85 KDa in the plasma of egg layers has been confirmed, but this does not apply to other animals (see, Lindquist, S., Annu. Rev. Biochem., (1986); Morimoto, R. I. and Milarski, K. L., Stress Proteins in Biology and Medicine, pp.323-359(1990); Siegel, H. S., Br. Poult. Sci., 36, 3-22 (1995)).
Reducing or preventing the production of stress proteins in the biophylaxis reaction is a very important issue for healthy and effective breeding of animals. Thus, there has been a demand for the development of a method for controlling and reducing the stress reaction.
When an animal is placed under stress, the stress reaction such as an increase or fluctuation in LDH, MDH or AspAT in blood is observed. However, in many cases, the stress phenomenon capable of externally visual observation, such as a loss in body weight or a reduction in eggshell strength, is not generated and even when it appears, the phenomenon is very often recognized after the lapse of a fairly long time. However, when the stress reaction continues for a long period or when other stress reactions such as infectious diseases multiply, the stress of animals is gradually accumulated and amplified. This may cause serious disease or result in the deterioration of meat quality, egg quality or milk quality before the livestock manager becomes aware of the problem. In conventional techniques, a method capable of satisfactorily suppressing the stress reaction such as an increase or fluctuation of LDH, MDH or AspAT in blood has not been reported.
Thus, in recent highly and intensively efficient stockbreeding or poultry farming, awareness of the stress reaction that is not visually observable and a means for suppressing the same has been an important issue in view of the breeding control of healthy livestock. Furthermore, it has been found that the stress reaction is reliably detected by determining the LDH, MDH or AspAT in the blood of animals.
As described above, the increase of plasma LDH, MDH or AspAT and the increase of stress proteins in blood, as a stress reaction of animals, is a very important physiological index for stress. However, the proposals hitherto reported with respect to stress suppression include neither an anti-stress agent for animals capable of detecting and suppressing the stress reaction of useful livestock nor a method of reducing the stress of animals by administering such an anti-stress agent.
Furthermore, although a method of orally administering vitamin C to egg layers raised in a high temperature environment to increase eggshell strength has been reported, an overall method of preventing the stress imposed on a living animal by suppressing the increase of plasma LDH, MDH and AspAT and the increase of stress proteins in blood, as important physiological indices for stress, has not yet been found.